Seibyl John P
Institute for Neurodegenerative Disorders, New Haven, CT 06510, USA.
Semin Nucl Med. 2003 Apr;33(2):105-13. doi: 10.1053/snuc.2003.127303.
Imaging presynaptic dopaminergic markers provides key insights into the pathophysiology of Parkinson's Disease (PD) and is becoming an important endpoint in clinical trials of potential disease-modifying therapies for PD. The further development of this area includes work to optimize targets for accurate and reliable measurement of disease progression. Ultimately, it may be possible to elaborate these markers to fine-tune our understanding of those patients who might be enrolled in a trial. For example, PD patients may be characterized as slow vs. fast progressors based on imaging measures, providing the opportunity to optimize the trial recruitment to demonstrate the greatest impact in Phase 2 evaluations of neuroprotective agents. Further, while dopamine degeneration is a crucial feature of PD, it is clear that there is widespread degeneration in the brain in PD and that many clinical manifestations of PD are likely not due to dopamine deficiency. It is reasonable to imagine that the characterization of additional targets outside the dopamine system could aid in both the molecular basis for disease characterization and ultimately optimization of therapeutics.
对突触前多巴胺能标志物进行成像可为帕金森病（PD）的病理生理学提供关键见解，并且正成为PD潜在疾病修饰疗法临床试验中的一个重要终点。该领域的进一步发展包括致力于优化靶点，以准确可靠地测量疾病进展。最终，或许能够详细阐述这些标志物，以更精确地理解哪些患者可能适合纳入试验。例如，基于成像测量，PD患者可被分为疾病进展缓慢型和快速型，这为优化试验招募提供了机会，以便在神经保护剂的2期评估中展现出最大效果。此外，虽然多巴胺变性是PD的一个关键特征，但很明显，PD患者大脑中存在广泛的变性，而且PD的许多临床表现可能并非由多巴胺缺乏所致。可以合理推测，对多巴胺系统之外的其他靶点进行特征描述，有助于明确疾病特征的分子基础，并最终实现治疗方法的优化。
